Your body consists of trillions of cells. Inside each cell are many structures. The endoplasmic reticulum (ER) is a large, complex structure that makes and transports substances the cell needs, such as proteins and lipids (a group that includes fats). Lipids are made, in part, from molecules called fatty acids, which come from digested dietary fats. Various lipids and proteins make up the membrane around the ER, which is the largest membrane system inside a cell. This system controls the traffic of substances that are continuously moving into, within, and out of the ER.

Past research suggests that consuming unsaturated fatty acids, such as those found in fish and peanut butter, protects against certain diseases. In contrast, consuming saturated fatty acids, such as those in meat and cheese, can contribute to disease. Scientists have been developing imaging methods and other technologies to investigate on a molecular level how cells are helped or harmed by certain types of lipids.

A research team led by Dr. Wei Min at Columbia University developed an advanced microscope technique to visualize small molecules in living cells. The technique relies on an approach known as stimulated Raman scattering. The team used the technique to determine how saturated and unsaturated fatty acids become incorporated into the ER membranes of living cells. The research was supported in part by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and an NIH Director’s New Innovator Award. Results appeared online on December 1, 2017, in Proceedings of the National Academy of Sciences.

After exposing human cells in the laboratory to a saturated fatty acid known as palmitate, the team discovered that the ER membrane was not entirely flexible and fluid. A fluid, flexible membrane allows for the ER to do its work, such as the easy transport of substances in and out of the ER. Instead, the ER membrane now had stiff, solid-like patches.

Next, the team showed that a common unsaturated fatty acid known as oleate did not form stiff portions after being incorporated into the membrane. When both oleate and palmitate were added to living cells, fewer stiff portions were observed than with palmitate alone. A polyunsaturated fatty acid also had the same beneficial effect as oleate. These findings may reveal one way that consuming a high level of saturated fat contributes to cell damage—and how unsaturated fat counteracts the damage.

“The behavior of saturated fatty acids once they’ve entered cells contributes to major and often deadly diseases,” Min says. “Visualizing how fatty acids are contributing to lipid metabolic disease gives us the direct physical information we need to begin looking for effective ways to treat them. Perhaps, for example, we can find a way to block the toxic lipid accumulation.”

Funding: NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institute of Neurological Disorders and Stroke (NINDS); NIH Director’s New Innovator Award; and the Camille and Henry Dreyfus Foundation.